Interference with its oxygen supply is the major stress which the fetus encounters in utero. Our aim is to understand the fetal cardiovascular response to hypoxemia, to assess this response with increasing gestational age, and to study the role of autonomic nervous control during hypoxemia, the fetal lambs from mid-gestation through birth. Previous studies of fetal circulation during asphyxia were done acutely and did not separate the effects of hypoxemia from acidemia or asphyxia. We have examined the cardiovascular response to hypoxemia in chronic fetal preparations. Fetal and maternal hypoxemia are produced by administering low oxygen gas mixtures to the unanesthetized standing ewe. Fetal and maternal heart rate, arterial pressures, oxygen contents and blood gases are repeatedly measured. Simultaneous blood flows to all fetal tissues are measured, using radionuclide-labelled microspheres during the control, hypoxemic, and recovery states. We are also studying the effects of alpha- and beta-adrenergic and parasympathetic stimulation during hypoxemia, by means of selective pharmacologic blockade. These studies should clarify the pattern of developing autonomic nervous control over the fetal circulation during hypoxemia, and provide a physiologic background from which we may improve our management of fetal asphyxia.